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Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Study Objectives: This study aimed to identify the risk factors associated with falls in hospitalized patients, develop a predictive risk model using machine learning algorithms, and evaluate the validity of the model's predictions., Study Design: A cross-sectional design was employed using data from the DRYAD public database., Research Methods: The study utilized data from the Fukushima Medical University Hospital Cohort Study, obtained from the DRYAD public database. 20% of the dataset was allocated as an independent test set, while the remaining 80% was utilized for training and validation. To address data imbalance in binary variables, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors (SMOTE-ENN) was applied. Univariate analysis and least absolute shrinkage and selection operator (LASSO) regression were used to analyze and screen variables. Predictive models were constructed by integrating key clinical features, and eight machine learning algorithms were evaluated to identify the most effective model. Additionally, SHAP (Shapley Additive Explanations) was used to interpret the predictive models and rank the importance of risk factors., Results: The final model included the following variables: Adl_standing, Adl_evacuation, Age_group, Planned_surgery, Wheelchair, History_of_falls, Hypnotic_drugs, Psychotropic_drugs, and Remote_caring_system. Among the evaluated models, the Random Forest algorithm demonstrated superior performance, achieving an AUC of 0.814 (95% CI: 0.802-0.827) in the training set, 0.781 (95% CI: 0.740-0.821) in the validation set, and 0.795 (95% CI: 0.770-0.820) in the test set., Conclusion: Machine learning algorithms, particularly Random Forest, are effective in predicting fall risk among hospitalized patients. These findings can significantly enhance fall prevention strategies within healthcare settings., Competing Interests: Declarations. Ethics approval and consent to participate: This study involving human participants was reviewed and approved by the Ethics Committee of The West China Fourth Hospital of Sichuan University. Written informed consent was waived in accordance with national regulations (Article 32 of the Regulation on the Administration of Medical Institutions of China). Consent for publication: Not applicable. This manuscript does not contain any individual person’s data, including any personal details, images, or videos. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: At present, the influencing factors of social function in patients with residual depressive symptoms are still unclear. Residual depressive symptoms are highly harmful, leading to low mood in patients, affecting work and interpersonal communication, increasing the risk of recurrence, and adding to the burden on families. Studying the influencing factors of their social function is of great significance., Aim: To explore the social function score and its influencing factors in patients with residual depressive symptoms., Methods: This observational study surveyed patients with residual depressive symptoms (case group) and healthy patients undergoing physical examinations (control group). Participants were admitted between January 2022 and December 2023. Social functioning was assessed using the Sheehan Disability Scale (SDS), and scores were compared between groups. Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve, and these factors' predictive efficacy on social function impairment was assessed., Results: The SDS scores of the 158 patients with depressive symptoms were 11.48 ± 3.26. Compared with the control group, the SDS scores and all items in the case group were higher. SDS scores were higher in patients with relapse, discontinuous medication, drug therapy alone, severe somatic symptoms, obvious residual symptoms, and anxiety scores ≥ 8. Disease history, medication compliance, therapy method, and residual symptoms correlated positively with SDS scores ( r = 0.354, 0.414, 0.602, and 0.456, respectively). Independent influencing factors included disease history, medication compliance, therapy method, somatic symptoms, residual symptoms, and anxiety scores ( P < 0.05). The areas under the curve for predicting social functional impairment using these factors were 0.713, 0.559, 0.684, 0.729, 0.668, and 0.628, respectively, with sensitivities of 79.2%, 61.8%, 76.8%, 81.7%, 63.6%, and 65.5% and specificities of 83.3%, 87.5%, 82.6%, 83.3%, 86.7%, and 92.1%, respectively., Conclusion: The social function scores of patients with residual symptoms of depression are high. They are affected by disease history, medication compliance, therapy method, degree of somatic symptoms, residual symptoms, and anxiety., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

With the widespread application of the Internet, network security issues have become increasingly prominent. As an important infrastructure of the Internet, the domain name server has been attacked in various forms. Traditional methods for detecting malicious domain servers are usually based on rules or feature engineering, requiring a large amount of manual participation and rule library updates. These methods cannot adapt to the constantly changing threat environment. In response to these issues, this study first improves the Transformer by adjusting its attention head and encoding method. Then, the model is combined with convolutional neural networks. Finally, a block-based ensemble classifier is used for classification detection. The relevant outcomes showed that the average accuracy score of the proposed method was as high as 95.8 points, the average detection time score was 96.8 points, the average feature extraction ability score of the model was 96.3 points, and the overall performance score was 97.6 points. This method has significant advantages over traditional methods in terms of accuracy and detection time, providing a new tool for detecting malicious domain servers., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain are the main pathological changes in Parkinson's disease (PD); however, the mechanism underlying the selective vulnerability of specific neuronal populations in PD remains unclear. Here, we used single-cell RNA sequencing to identify seven cell clusters, including oligodendrocytes, neurons, astrocytes, oligodendrocyte progenitor cells, microglia, synapse-rich cells (SRCs), and endothelial cells, in the substantia nigra of a rotenone-induced rat model of PD based on marker genes and functional definitions. We found that SRCs were a previously unidentified cell subtype, and the tight interactions between SRCs and other cell populations can be improved by icaritin, which is a flavonoid extracted from Epimedium sagittatum Maxim. and exerts anti-neuroinflammatory, antioxidant, and immune-improving effects in PD. We also demonstrated that icaritin bound with transcription factors of SRCs, and icaritin application modulated synaptic characterization of SRCs, neuroinflammation, oxidative stress, and survival of dopaminergic neurons, and improved abnormal energy metabolism, amino acid metabolism, and phospholipase D metabolism of astrocytes in the substantia nigra of rats with PD. Moreover, icaritin supplementation also promotes the recovery of the physiological homeostasis of the other cell clusters to delay the pathogenesis of PD. These data uncovered previously unknown cellular diversity in a rat model of Parkinson's disease and provide insights into the promising therapeutic potential of icaritin in PD.

In this work, a highly efficient rongalite/iodine-mediated oxime formation reaction for the preparation of thiohydroximic acids from methyl ketones by employing copper nitrate as the [NO] reagent has been developed. Notably, copper nitrate participated as both a catalyst and the mild oximation reagent in the transformation. This reaction is highly efficient and facile, with a broad substrate scope, especially for fused ring skeleton substrates, heterocyclic skeleton substrates, and acetyl-substituted natural products. Mechanistic studies revealed that copper nitrate might be converted into a NO 2 radical or the NO 2 radical dimeric forms as an ion-pair equivalent to participate in the transformation.

Background: Ovarian cancer (OC) remains the deadliest gynecologic malignancy worldwide due to delayed diagnosis, recurrence, and drug resistance. This study aimed to identify key factors affecting delayed diagnosis in OC patients., Methods: A retrospective analysis was conducted on OC patients treated at Taihe Hospital, Hubei University of Medicine from June 2023 to September 2023. Patients were categorized based on a three-months cut-off point for delayed diagnosis. Collected data included demographics, tumor incidence, and disease cognition. The analysis of variance and the chi-squared test was used for comparison between groups., Results: The significant differences were found in age, residence, education level, family income, family history of tumor, histology, FIGO stage, and tumor location between groups ( P <0.05). Multifactorial logistic regression analysis identified education level [odds ratio (OR) = 0.606; 95% confidence interval (CI): 0.440, 0.833; P = 0.002], family history of tumor (OR = 0.462; 95% CI: 0.214, 0.997; P = 0.049), emotional barriers (OR = 1.332; 95% CI: 1.081, 1.642; P = 0.007), and practical barriers (OR = 2.964; 95% CI: 2.195, 4.004; P < 0.001) as risk factors for delayed diagnosis of OC., Conclusion: Patient cognition is crucial in OC diagnosis delay. Enhancing public awareness and understanding of OC is essential to eliminate fear and improve early diagnosis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Hong et al.)

Congenital anomalies of the kidney and urinary tract (CAKUT) are primarily causal for end-stage renal disease and have significant implications for long-term survival. A total of 39 healthy controls and 94 children with chronic kidney disease (CKD) were enrolled (3-12 years old as children, 13-18 years old as adolescents), who were divided into CAKUT and Non-CAKUT according to the etiology of CKD. CKD group was further classified according to estimating glomerular filtration rate (eGFR). Circulating levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemokine-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) were analyzed. The relationship between these inflammatory markers with eGFR and the kidney injury parameter (urine protein) was investigated to assess their potential as early markers of disease progression. All circulating levels of these inflammatory cytokines were increased in CKD patients (including CAKUT and Non-CAKUT) compared with healthy subjects. The circulating levels of MCP-1 and TGF-β1 were increased in CAKUT adolescents compared with CAKUT children. In CAKUT children, levels of MCP-1 and TGF-β1 increased as CKD progressed, and MCP-1 and TGF-β1 were negatively and significantly correlated with eGFR and positively with urine protein. MCP-1 and TGF-β1 may contribute to the early detection of CKD and disease stage/progression in CAKUT children., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The present study was approved by the Ethics Committee of WuXi Children’s Hospital and written informed consent was provided by all patients prior to the study start. All procedures were performed in accordance with the ethical standards of the Institutional Review Board and The Declaration of Helsinki, and its later amendments or comparable ethical standards. Competing Interests: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Increasing evidence supports the association between impaired oral health and elevated mortality. However, there is currently a lack of research on the impact of tooth loss and periodontal disease on survival outcomes in cancer survivors. This study aims to clarify the effect of tooth loss and periodontitis on all-cause mortality on cancer survivors., Methods: The clinical data of cancer survivors were collected from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality data were obtained by linking to records in the National Death Index until December 31, 2019. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold for discriminating mortality based on the number of teeth lost. Kaplan-Meier survival curves and Cox regression analysis were performed to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CI) for tooth loss and periodontitis., Results: A total of 3271 cancer survivors were assessed for tooth loss status, while 1267 patients were evaluated for periodontitis status. The prevalence of any tooth loss and CDC-AAP periodontitis was 83.5 % and 47.2 %, respectively. The ROC curve showed the cut-off point of tooth loss for predicting mortality is > 5. Cancer survivors with tooth loss>5 had significantly lower bone density (1.06 vs. 1.13 g/cm 2 , P  < 0.001), elevated C-reactive protein level (0.3 vs. 0.18 mg/dL, P  < 0.001), and a trend of lower lean body mass (46.9 vs. 47.6 kg, P  = 0.093). Besides, cancer survivors with severe periodontitis also exhibited elevated C-reactive protein level (0.34 vs. 0.21 mg/dL, P  = 0.033). All-cause mortality significantly increased in cancer survivors with either tooth loss>5 (HR = 1.290, P  = 0.001) or severe CDC-AAP periodontitis (HR = 1.682, P  = 0.016) in the multivariate Cox regression analysis., Conclusion: Tooth loss and periodontitis are strong risk factors for reduced overall survival in cancer survivors. Cancer survivors should emphasize diligent oral hygiene and consistent dental check-ups to optimize long-term oral health. The causal relationship between oral health and survival rates in cancer survivors requires further validation through randomized controlled trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The release of carbon disulfide can have adverse effects on our environment and human health. The stability of carbon disulfide and the slow kinetics of hydrolysis can make it challenging to achieve efficient and practical cleavage of the CS bonds. Herein, a calix[4]arene-based porous organic polymer (CPOP-1) is innovatively synthesized through an optimized polycondensation reaction using C-Methylcalix[4]resorcinarene and hexafluoro-hexaazatriphenylene as monomers. Subsequently, palladium-induced calix[4]arene-based porous organic polymer was also synthesized via strong Pd-N coordination bonds to construct the metal-induced porous catalyst (CPOP-2). The polymeric catalyst active center [Pd 2+ (N^N)(NO 3 - ) 2 ] demonstrated outstanding catalytic hydrolysis performance (11.14 μmol g -1 h -1 ) in 10.5 h which is significantly enhanced by ca.13.2 times as compared to reported mononuclear Bpy-Pd(NO 3 ) 2 , and 7.07 times than model trinuclear complex catalyst HATN-Pd-1, respectively. The control experiments revealed that POP catalysts showcased robust stability, prolonged effectiveness, and feasible recyclability during the hydrolytic cleavage of carbon disulfide at room temperature in aqueous solutions. Furthermore, the coordination environment of [Pd 2+ (N^N)] was validated through XPS, EXAFS, and isotope labeling measurements, and the hydrolysis cleavage products were confirmed e. g. CO 2 , sulfide, and protons. More importantly, a reaction mechanism was formulated coupled with theoretical calculations, and simulations. The proposed mechanism involves sequential OH - nucleophilic attacks on the carbon atoms of insert-coordinated CS 2 and COS, leading to the cleavage of double CS bonds and the formation of CO bonds. The concurrent dissociation of the C-S bond and liberation of CO 2 result in an intermediate structure characterized by [(N^N)Pd 2+ ](SH - ) 2 . This intermediate motif serves as the source of the thermodynamic driving force for the reaction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Palladium-Anchored Calix[4]Arene-Derived Porous Organic Polymer Towards Efficient Hydrolytic Cleavage of Carbon Disulfide”. All authors have given approval to the final version of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: The primary objective of this study was to evaluate the safety and efficacy of the enhanced recovery after surgery (ERAS) protocol in cholecystectomy, comparing it with standard care. Methods: A comprehensive literature search was conducted in December 2023, using globally recognized databases such as PubMed, Embase, and the Cochrane Library. Various parameters were compared using Review Manager software. This study was duly registered with PROSPERO (CRD420223). Results: The meta-analysis included nine studies, encompassing a total of 1920 patients. The findings revealed that the ERAS group, in comparison to traditional care, experienced shorter hospitalization periods (weighted mean difference [WMD]: -1.23, 95% confidence interval [CI]: -1.98 to -0.47; P = .001), lower visual analog scale at 24 hours (WMD: -1.10, 95% CI: -1.30 to -0.90; P < .00001), faster time to first flatus (WMD: -4.48, 95% CI: -4.50 to -4.46; P < .00001), and reduced operative times (WMD: -9.94, 95% CI: -17.88 to -0.96; P = .03). In addition, there was a notable decrease in instances of postoperative nausea and vomiting (odds ratio [OR]: 0.46, 95% CI: 0.28 to 0.74; P = .002). No significant differences were observed in readmission rates, blood loss, postoperative complications, or bile leakage between the two care methods. Conclusions: This study substantiates that the ERAS protocol is an advantageous perioperative care strategy for patients undergoing cholecystectomy. It significantly outperforms traditional care in reducing the length of stay, decreasing the likelihood of postoperative nausea/vomiting, alleviating postoperative pain, and accelerating the time to the first flatus. These findings highlight the effectiveness of ERAS in enhancing patient outcomes in cholecystectomy.

Objective: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation., Methods: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions., Results: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ., Conclusions: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Soil molybdenum (Mo) levels can reach ecologically hazardous levels. China has not yet established the relevant thresholds, posing challenges for environmental management. Therefore, we present our data relevant to Mo toxicity for several important species. By normalizing soil properties, we obtained a correlation model of Mo toxicity to Hordeum vulgare, as well as 31 models for the toxicity of other elements including Cu and Ni to invertebrates and microbial processes. Using interspecies correlation estimation (ICE) extrapolation, the sensitivity coefficient (0.12-0.71) for five plants were found. For invertebrates and microbial processes lacking Mo data, we used regression analysis to establish Mo toxicity models based on the soil quantitative ion character-activity relationships (s-QICAR; R 2 =0.70-0.95) and known toxicities of other metal elements to invertebrate and microbial processes. Furthermore, combining species sensitivity distribution calculations, the HC 5 values for protecting 95% of soil species from Mo in three typical soil scenarios in China were calculated. After correction, the predicted no-effect concentrations were 6.8, 4.8, and 3.4 mg/kg, respectively. This study innovatively combined ICE and s - QICAR to derive soil Mo thresholds. Our results can provide a basis for decision-making in the assessment and management of soil Mo pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation., Methods: We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis., Results: Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes Cdc25A and Cdc2 . However, Sal A does not affect the Chk1-Cdc25C pathway., Conclusions: Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

In this work, a practical copper-catalyzed multicomponent coupling reaction of primary aromatic amines, rongalite, and alkynes for the direct synthesis of N -aryl propargylamines has been developed. This method could overcome the substrate limitation in A 3 coupling reactions of primary aromatic amines, formaldehyde, and alkynes. Mechanistic studies revealed that rongalite acts as not only the active C1 unit but also the accelerator to activate the in situ -generated N -arylmethanimines for the coupling reaction with alkynes. This coupling reaction is highly efficient and features a broad substrate scope, as well as utility with scale-up synthesis and converting the corresponding product N -aryl propargylamines into useful heterocyclic skeletons.

Two new monoterpene esters, illigerates H and I ( 1 and 2 ), and six known compounds actinodaphine ( 3 ), bulbocupnine ( 4 ), stephanine ( 5 ), hypserpanine B ( 6 ), betulinic acid ( 7 ) and gallic acid ( 8 ) were obtained from the root of Illigera paviflora Dunn. Their structures were elucidated by spectroscopic analysis. Anti-inflammatory and α-glucosidase inhibitory activity of some isolated compounds were assessed. Two monoterpenes 1 and 2 exhibited weak in vitro anti-inflammatory activity (IC 50 64.5 ± 5.3 and 79.2 ± 7.5 μM) while compounds 3-6 showed inhibition of α-glucosidase with IC 50 values ranged from 87.17 to 118.74 μM.

Neuropathic pain (NP) is a prevalent clinical problem for which satisfactory treatment options are unavailable. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore, possesses anti-inflammatory and immune-modulatory properties. Chemokine-like factor 1 (CKLF1) is known to play a crucial role in both peripheral and central inflammatory processes. This study aimed to investigate the potential anti-NP effects of TET and the involvement of CKLF1 in the action of TET. A male C57BL/6J mice model of NP caused by spared nerve injury (SNI) was established and mechanical withdrawal thresholds were measured using von Frey filaments. The results showed that TET improved mechanical allodynia in SNI mice and the propofol-induced sleep assay demonstrated that the TET group did not exhibit central inhibition, while the pregabalin (PGB) group showed significant central inhibition. Western blotting and immunofluorescence staining showed that TET significantly inhibited spinal protein expression levels of CKLF1, p-NF-κB/NF-κB, p-IKK/IKK, pro-inflammatory cytokines IL-1β and TNF-α, and increased protein expression levels of the anti-inflammatory cytokine IL-10, while inhibiting the expression levels of microglia and astrocyte markers IBA-1 and GFAP of SNI mice. Moreover, immunofluorescence double-labeling results revealed that CKLF1 was predominantly colocalized with microglia of the spinal cord (SC) in SNI mice. C19 (an antagonism peptide of CKLF1) alleviated SNI-induced mechanical pain hypersensitivity, while C27 (an analog peptide of CKLF1) induced mechanical allodynia in normal mice. TET significantly attenuated mechanical allodynia induced by C27 in mice. TET may effectively alleviate NP by reducing neuroinflammation and decreasing CKLF1., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Very high-resolution (VHR) remote sensing (RS) image classification is the fundamental task for RS image analysis and understanding. Recently, Transformer-based models demonstrated outstanding potential for learning high-order contextual relationships from natural images with general resolution ( ≈ 224 × 224 pixels) and achieved remarkable results on general image classification tasks. However, the complexity of the naive Transformer grows quadratically with the increase in image size, which prevents Transformer-based models from VHR RS image ( ≥ 500 × 500 pixels) classification and other computationally expensive downstream tasks. To this end, we propose to decompose the expensive self-attention (SA) into real and imaginary parts via discrete Fourier transform (DFT) and, therefore, propose an efficient complex SA (CSA) mechanism. Benefiting from the conjugated symmetric property of DFT, CSA is capable to model the high-order contextual information with less than half computations of naive SA. To overcome the gradient explosion in Fourier complex field, we replace the Softmax function with the carefully designed Logmax function to normalize the attention map of CSA and stabilize the gradient propagation. By stacking various layers of CSA blocks, we propose the Fourier complex Transformer (FCT) model to learn global contextual information from VHR aerial images following the hierarchical manners. Universal experiments conducted on commonly used RS classification datasets demonstrate the effectiveness and efficiency of FCT, especially on VHR RS images. The source code of FCT will be available at https://github.com/Gao-xiyuan/FCT.

Background: Regenerating gene (REG) family proteins play a pivotal role in cell proliferation, tissue regeneration, and tumor metastasis. Recent studies have concentrated on the role of REG proteins in pancreatic cancer, but the results remain controversial. In this study, a meta-analysis was performed to evaluate the precise diagnostic value of REG proteins in pancreatic cancer., Methods: A search was conducted in PubMed, Medline, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Biomedical Literature Database (CBM), and WANFANG Data up to May 5, 2021. The QUADAS-2 tool was used to evaluate the quality of the included studies. The statistical analysis of the diagnostic tests was conducted using RevMan5 and Meta-Disc 1.4. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CIs) were calculated from each eligible study., Results: The meta-analysis included 15 articles containing 796 patients and 584 controls. The pooled sensitivity was 0.71 (95% CI: 0.67 - 0.74), the pooled specificity was 0.73 (95% CI: 0.70 - 0.76), and the pooled DOR was 11.35 (95% CI: 5.92 - 21.77), respectively. The overall area under the receiver operating characteristic curve (AUC) was 0.84. Spearman's correlation coefficient was 0.34 (p = 0.221). For the subgroup analysis, the REG4 protein showed higher diagnostic accuracy compared with the other REG proteins., Conclusions: REG proteins have moderate diagnostic accuracy in pancreatic cancer. Further well-designed studies with larger sample sizes and clinical application are needed to validate the results of this meta-analysis.

Background: Gastric cancer (GC) is a malignant tumor with high morbidity and mortality. Expression of COL5A2 is significantly elevated in GC. Abnormal expression of noncoding RNAs (ncRNAs) have been found in GC, including microRNA (miRNA) and long noncoding RNA (lncRNA). Competing endogenous RNA network plays an important regulatory role in GC. However, its specific regulatory mechanism has not been elucidated., Aim: To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC., Methods: RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2 , miRNA and lncRNA related to the prognosis of GC. Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2 . StarBase was used to predict the interaction of miRNA-lncRNA or miRNA-mRNA in GC. The relationship between COL5A2 , miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay. The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis. The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining., Results: We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC. miR-144-3p was downregulated and correlated with the prognosis of GC. miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2 . ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p, thus inhibiting the expression of miR-144-3p. ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p. Compared to paired normal tissue, COL5A2 expression was upregulated at the protein level, especially in the middle and late stages of GC. The high expression of COL5A2 was positively linked to macrophage infiltration in GC., Conclusion: COL5A2 regulated by ENTPD1-AS1-miR-144-3p was associated with poor prognosis and macrophage infiltration in GC. This could be a new biomarker and therapeutic target in GC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Primary adenoid cystic carcinoma in the trachea (TACC) is a rare tumour. Tracheal bronchoscopy is always chosen as a routine approach to obtain a pathological diagnosis, but it can be associated with an increased risk of asphyxia., Case Summary: We describe a case of TACC in a patient evaluated by chest computed tomography (CT) with three-dimensional reconstruction imaging and diagnosed by transoesophageal endoscopic ultrasonography. The pathological diagnosis confirmed tracheal adenoid cystic carcinoma., Conclusion: We highlight the importance of CT and provide a successful exploration of transoesophageal biopsy as a safe alternative approach., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To analyse the characteristics and mortality of hypertrophic cardiomyopathy (HCM) patients with different body compositions., Methods: In this study, 530 consecutive patients with HCM at West China Hospital were studied from November 2008 to May 2016. An equation based on body mass index (BMI) was used to obtain the Percent body fat (BF) and lean mass index (LMI). Patients were divided into five sex-specific BMI, BF and LMI quintiles., Results: The average BMI, BF and LMI were 23.1 ± 3.2 kg/m 2 , 28.1 ± 7.3% and 16.5 ± 2.2 kg/m 2 , respectively. Patients with higher BMI or BF were older and had more symptoms and adverse cardiovascular conditions; those with higher LMI were younger and had less coronary artery disease and lower serum NT-proBNP and creatine. BF correlated positively with resting left ventricular (LV) outflow tract gradient, mitral regurgitation (MR) degree and left atrial diameter but was inversely associated with septal wall thickness (SWT), posterior wall thickness (PWT), LV mass, and E/A ratio; LMI was positively correlated with SWT, LV end diastolic volume and LV mass but was negatively associated with MR degree.48 all-cause deaths occurred during a median follow-up of 33.8 months. Reversed J-shape associations of BMI and LMI with mortality were observed. A lower BMI or LMI was significantly associated with high mortality, especially for low-moderate BMI and LMI. No significant difference in mortality was found across BF quintiles., Conclusions: The associations of BMI, BF and LMI with baseline characteristics and cardiac remodelling are different in HCM patients. In Chinese HCM patients, low BMI and LMI predicted mortality but not BF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou, Xiang, Li, Pu and Zhang.)

A 36-year-old female patient came to our hospital with the chief complaint of having white patches on her waist for 10-plus years and having new annular plaques appearing on the white patches for 6-plus months. Wood's lamp examination done in the hospital showed a positive result. Histopathology of skin tissue from the edge of the annular swelling on the right waist revealed epidermal hyperkeratosis, wedge-shaped thickening of the granular layer, liquefactive degeneration of the basal cells, and a band-like infiltration of lymphocytes in the superficial dermis. The patient was diagnosed with vitiligo combined with annular lichen planus (ALP). The patient was treated with topical halometasone cream administered twice a day. The purplish-red annular plagues subsided and disappeared almost completely one month after the treatment was started and no signs of recurrence were observed duringn the 2-month follow-up. ALP is a rare variant of lichen planus. There has been no reported case of vitiligo combined with ALP so far., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older., Methods: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome., Results: Over a median follow-up period of 1,176 d (interquartile range [IQR], 722-1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [ HR ]=1.81, 95% confidence interval [ CI ]: 1.03-3.20; P =0.040), but not in the low/minimal- (adjusted HR =1.29, 95% CI : 0.80-2.11; P =0.299) or intermediate-risk groups (adjusted HR =1.14, 95% CI : 0.65-2.02; P =0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P =0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups., Conclusions: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management., Competing Interests: Conflicts of interest: None., (Copyright: © World Journal of Emergency Medicine.)

Rationale: Streptococcus gordonii is a rare cause of finger suppurative infection. Very few cases have been reported of its treatment., Patient Concerns: A 68-year-old male of severe finger infection. Bacterial culture of synovial fluid revealed S gordonii.According to the patient's history and auxiliary examination, the patient was diagnosed with S gordonii infection. Here, we review the diagnosis and treatment of this patient and describe the clinical and epidemiological characteristics of the patient., Diagnoses: Streptococcus gordonii finger infection.Interventions: In the case of ineffective oral antibiotics, this patient chose to pursue an abscess incision, but in the course of treatment,the flexor digitorum tendon dissolved and eventually ruptured., Outcomes: The infection was controlled after intravenous injection of vancomycin. The incision was sutured 2 weeks later. No recurrence of infection was found after 3 months of follow-up., Lessons: The treatment included antibacterial and abscess treatments. In the absence of drug sensitivity results, antibiotics can be used empirically. If empirical anti-microbial treatment fails, the antibiotic regimen should be changed in a timely manner, Vancomycin may be an antibiotic choice., Competing Interests: The authors have no funding and conflict of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1β secretion in J771A.1 cells, revealed 28 compounds with an IC 50 below 10.5 μM. Compound 1 was the most potent with an IC 50 of 0.68 μM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative Au I ···Au I and Au-N interactions, the gold(I) clusters 1 + •BF 4 - and 2 4+ •4BF 4 - with Au 4 and Au 16 cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au 2 Cl 2 coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate-chloride/phosphine coordination substitution and Au-S/Au-N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 2 4+ •4BF 4 - exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 2 4+ •4BF 4 - changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.

Almost all genomes have orphan genes, the majority of which are not functionally annotated. There is growing evidence showed that orphan genes may play important roles in the environmental stress response of Physcomitrium patens. We identified PpARDT (ABA-responsive drought tolerance) as a moss-specific and ABA-responsive orphan gene in P. patens. PpARDT is mainly expressed during the gametophytic stage of the life cycle, and the expression was induced by different abiotic stresses. A PpARDT knockout (Ppardt) mutant showed reduced dehydration-rehydration tolerance, and the phenotype could be rescued by exogenous ABA. Meanwhile, transgenic Arabidopsis lines exhibiting heterologous expression of PpARDT were more sensitive to exogenous ABA than wild-type (Col-0) plants and showed enhanced drought tolerance. These indicate that PpARDT confers drought tolerance among land plants potentially by enhancing ABA response. Further, we identified genes encoding abscisic acid receptor PYR/PYL family proteins, and ADP-ribosylation factors (Arf) as hub genes associated with the Ppardt phenotype. Given the lineage-specific characteristics of PpARDT, our results provide insights into the roles of orphan gene in shaping lineage-specific adaptation possibly by recruiting common pre-existed pathway components., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Flame retardancy and recyclability are two important issues in the research field of thermosets, particularly for epoxy resin (EP) with the biggest market share. It is of great importance, but rarely achievable, to integrate these properties simultaneously into EP. Herein, we report a facile way to prepare intrinsically flame-retardant epoxy vitrimers combining rapid recycling and multiple shape memory effects by introducing dynamic ester-linkages with catalytic transesterification activity into the crosslinking networks of EP. The flame-retardant epoxy vitrimers exhibited high T g (∼110.7 °C), desirable thermal stability and excellent flame retardancy with UL-94 V-0 rating, and high LOI of ∼34%. Also, the value of the peak heat release rate (PHRR) and the total heat release (THR) showed 63% and 32% reduction, respectively. Meanwhile, flame-retardant epoxy vitrimers showed high malleability that could be reprocessed in 15 min at 200 °C without sacrificing the mechanical properties and flame retardancy. Moreover, the dynamic transesterification network allowed flame-retardant EP to access multiple shape memory effect. The design of flame-retardant epoxy vitrimers provide a prime example to foster the cyclic utilization of flame-retardant thermosetting polymers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Regional concentrations, fluorescent components, and sources of dissolved organic matter (DOM) in a drinking water source in Chaobai River across seasons were investigated here using fluorescence excitation-emission matrices, parallel factor analysis, and fluorescence indexes. Five fluorescent-DOM components were identified, including two microbial humic-like components and one autochthonous tyrosine-like, one reduced quinone-like, and one terrestrial humic-like component. DOM was mainly derived from microorganisms. The farmland-dominated region showed the highest DOM concentration and significantly lower maximum fluorescence intensities ( F max ) of almost all fluorescent components than those in the forest-dominated region. The region dominated by urban lands exhibited obviously lower DOM concentrations than those in the farmland-dominated region and lower F max values of fluorescent components than those in the forest-dominated region. No interaction was found between land use and season when considering their effects on DOM. Season had a significant influence on the humification degree of DOM. This study shows that agricultural land use had a greater impact on DOM than that of forests and urban areas, and the increased riverine DOM resulting from farmland was mainly non-fluorescent parts.

Background: Left ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD)., Methods: In this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using established formulas. Patients were grouped according to body fat percentage and presence or absence of LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death., Results: Of 2243 patients enrolled, 560 (25%) had a higher body fat percentage, and 1045 (46.6%) had LVH. After a median follow-up of 2.2 years, the cumulative mortality rate was 8.2% in the group with higher body fat and LVH, 2.5% in those with lower body fat and no LVH, 5.4% in those with higher body fat and no LVH, and 7.8% in those with lower body fat and LVH (log-rank P < 0.001). There was a statistically significant interaction between body fat percentage and LVH ( P interaction was 0.003). After correcting for confounding factors, patients with higher body fat and LVH had the highest risk of all-cause death (HR = 3.49, 95% CI: 1.40-8.69, P = 0.007) compared with those with lower body fat and no LVH; in contrast, patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH (HR = 2.03, 95% CI: 0.70-5.92, P = 0.195)., Conclusion: A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD, stratified by coexistence of LVH or not. Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH., (Copyright and License information: Journal of Geriatric Cardiology 2022.)

We present a chip-scale integrated pH sensor with high sensitivity by using an optofluidic ring resonator (OFRR) laser. An optical fiber with a high refractive index (RI) is employed both as an optical cavity and the sensing reactor along a microchannel, while disodium fluorescein (DSF) aqueous solution with a low RI is served as the cladding gain medium and fluorescent probes. The pump light is introduced along the fiber axis and guided by the total internal reflection at the fiber/cladding interface. The evanescent field of the pump light extends out of the fiber surface and efficiently excites the dye molecules residing in the evanescent field region of the Whispering Gallery Modes (WGMs) of the OFRRs to produce lasing emission. This pumping scheme provides a uniform excitation to the gain medium and significantly increases the signal-to-noise ratio, ensuring a low lasing threshold and highly sensitive sensing. The lasing threshold property under different pH conditions is experimentally and theoretically conducted to evaluate the sensing performance, which shows that the lasing threshold highly depends on the pH value of the cladding solution due to the increasing deprotonation process. We further verify that the intensity of the lasing emission and the pH value shows good linearity in the pH range 6.51-8.13, with a 2-order-of-magnitude sensitivity enhancement compared to fluorescence measurement. The proposed OFRR lasing platform shows excellent robustness and low sample consumption, providing a powerful sensing strategy in medicine, and hazardous/toxic/volatile sensing, which require label-free, real-time, and in situ detection.

Chilling stress at booting stage can cause floret deterioration and sterility by limiting the supply of food chain and the accumulation of essential mineral elements resulting in reduction of yield and grain quality attributes in rice. Genomic selection of chilling tolerant rice with reference to the accumulation of mineral elements will have great potential to cope with malnutrition and food security in times of climate change. Therefore, a study was conducted to explore the genomic determinants of cold tolerance and mineral elements content in near-isogenic lines (NILs) of japonica rice subjected to chilling stress at flowering stage. Detailed morphological analysis followed by quantitative analysis of 17 mineral elements revealed that the content of phosphorus (P, 3,253 mg/kg) and potassium (K, 2,485 mg/kg) were highest while strontium (Sr, 0.26 mg/kg) and boron (B, 0.34 mg/kg) were lowest among the mineral elements. The correlation analysis revealed extremely positive correlation of phosphorus (P) and copper (Cu) with most of the cold tolerance traits. Among all the effective ear and the second leaf length correlation was significant with half of the mineral elements. As a result of comparative analysis, some QTLs ( qBRCC-1 , qBRCIC-2, qBRZC-6 , qBRCHC-6 , qBRMC-6 , qBRCIC-6a, qBRCIC-6b, qBRCHC-6, and qBRMC-6 ) identified for calcium (Ca), zinc (Zn), chromium (Cr) and magnesium (Mg) on chromosome number 1, 2, and 6 while, a novel QTL ( qBCPC-1 ) was identified on chromosome number 1 for P element only. These findings provided bases for the identification of candidate genes involved in mineral accumulation and cold tolerance in rice at booting stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ali, Sun, Yang, Pu, Duan, Li, Wang, Yang and Zeng.)

In this study, the complete chloroplast (cp) genome of Narcissus tazetta var. chinensis cv 'Yulinglong' was sequenced and assembled by next-generation sequencing. The complete cp genome is 159,376 in length and contained 137 genes, consisting of 91 protein-coding genes, eight ribosomal RNA genes, and 38 transfer RNA genes. Phylogenetic analyses based on chloroplast genomes highly supported that 'Yulinglong' was evolutionarily close to Narcissus tazetta subsp. chinensis , which may provide more desirable information for the phylogenetic relationship between Narcissus tazetta var. chinensis and its relative species., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Neuroinflammation, oxidative stress, and mitochondrial dysfunction are all important pathogenic mechanisms underlying motor dysfunction and dopaminergic neuronal damage observed in patients with Parkinson's disease (PD). However, despite extensive efforts, targeting inflammation and oxidative stress using various approaches has not led to meaningful clinical outcomes, and mitochondrial enhancers have also failed to convincingly achieve disease-modifying effects. We tested our hypothesis that treatment approaches in PD should simultaneously reduce neuroinflammation, oxidative stress, and improve alterations in neuronal energy metabolism using the flavonoid icaritin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), coupled with biochemical analyses and behavioral tests, we demonstrate that icaritin improves PD by attenuating the the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activity and stabilizing mitochondrial function, based on our extensive analyses showing the inhibition of NLRP3 inflammasome, reduction of NLRP3-mediated IL-1β secretion, and improvements in the levels of antioxidant molecules. Our data also indicated that icaritin stabilized the levels of proteins related to mitochondrial function, such as voltage-dependent anion channel (VDAC) and ATP synthase subunit beta (ATP5B), as well as those of molecules related to energy metabolism, such as ATP and ADP, ultimately improving mitochondrial dysfunction. By employing molecular docking, we also discovered that icaritin can interact with NLRP3, VDAC, ATP5B, and several blood-brain barrier (BBB)-related proteins. These data provide insights into the promising therapeutic potential of icaritin in PD.

Background: Thymic-enteric adenocarcinoma with positive expression of CDX2 and CK20 is rare in adults, with only 16 reported cases. However, standard treatment options for this type of thymic adenocarcinoma has not yet been established. Therefore, we report a case of stage IV thymic-enteric adenocarcinoma treated with radiotherapy, chemotherapy, and anti-angiogenesis therapy., Case Summary: We report a case of thymic-enteric adenocarcinoma occurring in a 44-year-old woman. The tumor was considered unresectable owing to its invasiveness. The patient was treated with six cycles of oxaliplatin (130 mg/m 2 , day 1) and capecitabine (1000 mg/m 2 BID, days 1-14). During the first three cycles of chemotherapy, concurrent radiotherapy (60 Gy/30 fractions) and anti-angiogenic therapy using apatinib were recommended. The primary tumor achieved partial remission based on the Response Evaluation Criteria in Solid Tumors. During follow-up, there was no evidence of disease relapse, except a high serum CA19-9 level. The patient is alive and regularly followed. Based on the previous literature and the present case, we believe that early diagnosis of thymic-enteric adenocarcinoma is important., Conclusion: XELOX (capecitabine plus oxaliplatin) combined with radiotherapy is an optional therapy for inoperable thymic-enteric adenocarcinoma., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two new monoterpene esters illigerates F and G ( 1 and 2 ) together with 5 know compounds illigerate A ( 3 ), illigerate C ( 4 ), actinodaphnine ( 5 ), N-methylactinodaphnine( 6 ) and N-methyllaurotetanine( 7 ) were isolated from Illigera aromatica S. Z. Huang et S. L. Mo. Their structures were identified by extensive NMR data and by comparing with the known compounds. The anti-inflammatory activity of four monoterpenes ( 1 - 4 ) was evaluated by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells and four monoterpenoids exhibited inhibitory effect with IC 50 values of 71.5 ± 7.3, 74.7 ± 5.6, 48.0 ± 7.4 and 65.1 ± 3.7 μM, respectively.

Background: Notoginseng leaf triterpenes (PNGL) is believed to have neuroprotective effects via the inhibition of inflammatory response and neuronal apoptosis. However, its mechanisms underlying the anti-ischemia/reperfusion (I/R) injury effects on the regulation of small molecule metabolism in rat brain remains unclear. The purpose of this study was thus to explore the mechanisms of PNGL on the regulation of small molecule metabolism in rat brain after I/R injury using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI)., Methods: As a model of in vivo cerebral I/R injury, male Sprague-Dawley (SD) rats were established with a middle cerebral artery occlusion/reperfusion (MCAO/R) model after PNGL administration with 40 mg·kg -1 through intraperitoneal injection (i.p.) for 7 days. We assessed the neurological behavior, regional cerebral blood flow (r CBF), neuron injury, and spatial distribution of metabolic small molecules., Results: Our in vivo results suggested that PNGL increased cerebral blood flow and relieved neurological dysfunction. Furthermore, using MALDI-MSI, we demonstrated that PNGL regulated 16 endogenous small molecules implicated in metabolic networks including tricarboxylic acid (TCA) cycle, adenosine triphosphate (ATP) metabolism, malate-aspartate shuttle, metal ions, and antioxidants underwent noticeable changes after reperfusion for 24 h., Conclusions: PNGL is a novel cerebrovascular agent that can improve cerebral blood flow and attenuate adverse neurological disorders. The mechanisms are closely correlated with relative metabolic pathways, which offers insight into exploring new mechanisms in PNGL for the treatment of cerebral I/R injury., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4898). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Purpose: To observe the morphology of the transverse geniculate ligament of the knee (TGL) by magnetic resonance imaging (MRI) and to analyze the cause of the pseudotear sign of the anterior horn of the meniscus caused by the TGL., Methods: Patients who underwent MRI examination of the knee joint in the orthopaedics department of our hospital from July 2016 to August 2019 were identified. The occurrence rate, length, width, thickness, cross-sectional shape, pattern, appearance, and position relative to the anterior horn of the lateral and medial meniscus and anatomical variations were observed by multiplane and multisequence MRI. The frequency and cause of the pseudotear sign also were observed., Results: The data of 101 patients were analyzed. Among them, 60 were male, and 41 were female. The average age was 42.01 (18-75) years. The occurrence rate of the TGL was 67.3% (68/101), the average length was 38.75 ± 3.56 mm, the median coronal diameter was 1.79 ± 0.60 mm, the median sagittal diameter was 1.88 ± 0.35 mm, and the cross-sectional morphology was mostly oval and round. There were 5 types of TGL connection to the anterior horn of the medial meniscus: type 1, located at the front edge; type 2, located at the upper front edge; type 3, located at the upper edge; type 4, located at the back upper edge; and type 5, was located at the back edge of the anterior horn of the medial meniscus. There was only one type of TGL insertion into the anterior horn of the lateral meniscus, located at the anterior superior edge of the anterior horn of the lateral meniscus. There were 4 cases of the pseudotear sign in the anterior horn of the meniscus, 3 in the lateral meniscus and 1 in the medial meniscus. The pseudotear sign of the anterior horn of the meniscus caused by the TGL was observed at a rate of 5.88% (4/68)., Conclusions: In MRI examination of the knee, the anterior horn of the meniscus sometimes shows a pseudotear sign. According to the shape and route of the TGL on MRI and the direction and position of the pseudotear sign of the anterior horn of the meniscus, true and false tears of the anterior horn of the meniscus can be identified., Level of Evidence: Level III, diagnostic study (retrospective, noncomparative, observational case series without a consistently applied reference "gold" standard)., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gender plays a crucial role in the prevalence, clinical presentation, management and outcomes of various cardiovascular diseases. The aim of this study was to evaluate the impact of gender on clinical manifestations and outcomes in the Chinese patients with hypertrophic cardiomyopathy (HCM)., Methods: We evaluated 576 Chinese patients (316 males) who were diagnosed with HCM at West China Hospital from 2008 to 2016 and followed over 3.2 ± 2.3 years., Results: Compared to male patients, female patients were older (57.2 ± 16.7 years vs. 53.0 ± 15.7 years, P = 0.002) and more symptomatic [New York Heart Association class III-IV symptoms 46.9% vs. 30.7%, P < 0.001] at the time of diagnosis, and had higher left ventricular outflow tract gradient at rest [33 (12-58) mmHg vs. 24 (8-42) mmHg, P = 0.007]. During the follow-up period, survival analysis showed no significant differences in the incidences of all-cause mortality (P = 0.657) and cardiovascular mortality (P = 0.214) but the rate of rehospitalization due to heart failure was higher in females than in males (P = 0.015). Multivariable Cox analysis showed that left ventricular ejection fraction (hazard ratio [HR], 0.96 [95% confidence interval [CI], 0.94-0.99]; P = 0.003) and New York Heart Association class III-IV (HR, 2.86 [95% CI, 1.38-5.94]; P = 0.005) were independently associated with cardiovascular mortality., Conclusions: Compared to males, females were older and more symptomatic at presentation, and had higher risk of progression to heart failure in Chinese HCM patients but there were no differences in cardiovascular mortality., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years., Methods: 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months., Results: The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032)., Conclusions: DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ischemic stroke is a syndrome of severe neurological responses that cause neuronal death, damage to the neurovascular unit and inflammation. Notoginsenoside R1 (NG-R1) is a neuroprotective drug that is commonly used to treat neurodegenerative and cerebrovascular diseases. However, its potential mechanisms on the regulation of small molecule metabolism in ischemic stroke are largely unknown. The aim of this study was to explore the potential mechanisms of NG-R1 on the regulation of small molecule metabolism after ischemic stroke. Here, we found that NG-R1 reduced infarct size and improved neurological deficits by ameliorating neuronal damage and inhibiting glial activation in MCAO/R rats. Furthermore, using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), we clarified that NG-R1 regulated ATP metabolism, the tricarboxylic acid (TCA) cycle, the malate-aspartate shuttle, antioxidant activity, and the homeostasis of iron and phospholipids in the striatum and hippocampus of middle cerebral artery occlusion/reperfusion (MCAO/R) rats. In general, NG-R1 is a promising compound for brain protection from ischemic/reperfusion injury, possibly through the regulation of brain small molecule metabolism., (Copyright © 2020. Published by Elsevier Masson SAS.)

Three new flavonoids, quercetin-3- O -6-[methyl-( S )-3-hydroxy-3-methylglutaroyl(1→6]-β-d-glucopyranoside ( 1 ), kaempferol-3- O -[methyl-( S )-3-hydroxy-3-methylglutaroyl(1→6)]-β-d-glucopyranoside ( 2 ), and quercetin-3- O -6-[( E )-4-methoxy-5-methylhexa-2,4-dienoatyl(1→6)]-β-d-glucopyranoside ( 3 ), and two new alkaloids, 5-dehydroxymethyl-pyrrolemarumine 4″- O -α-l-rhamnopyranoside ( 4 ) and N 1 -methyl- N 2 -((4- O -α-l-rhamnopyranoside)benzyl) oxalamide ( 5 ), together with 45 known compounds ( 6 - 50 ) were isolated from the leaves of Moringa oleifera Lam. Among those compounds, 1-octacosanol ( 50 ), a straight-chain 28-carbon alcohol, exhibited good activity against diphenoxylate-induced constipation in mice, which is obtained as a laxative constituent from the plant for the first time. In order to have an accurate understanding of the content of compound 50 , a quantification with gas chromatography-tandem mass spectrometry (GC-MS/MS) was carried out. The anti-inflammatory and α-glucosidase inhibitory activity of some compounds also was assessed.

Soft tissue leiomyosarcoma (STLMS) is a major histological subtype of adult sarcoma. Although the molecular mechanisms ofLMS have been gradually revealed, no valid therapeutic targets have been identified. In this study, we performed a systematic screening to explore relapse-associated genes in STLMS, using data from The Cancer Genome Atlas-Sarcoma (TCGA-SARC). Then, we investigated the functional role of the gene with the best relapse-prediction value in STLMS by both in-vitro and in-vivo studies. Results showed that AMH and PLA2G10 were two genes with area under curve (AUC) values higher than 0.80 in ROC analysis when detecting relapse. Patients in the high AMH or PLA2G10 expression group had significantly worse relapse-free survival (RFS) compared to the respective low expression group. PLA2G10 was highly expressed in STLMS, but not in other sarcoma subtypes. PLA2G10 overexpression promoted SK-LMS-1 cell growth and G1/S transition, while PLA2G10 knockdown slowed the growth and resulted in G1 phase arrest. PLA2G10 overexpression markedly increased the expression of CDK2 and cyclin E1, but did not influence CDK4, CDK6, cyclin D1, CDK1 or cyclin A expression. PLA2G10 overexpression enhanced SK-LMS-1 cell-derived xenograft tumor growth in nude mice, while PLA2G10 inhibition slowed the growth. Mutation of two critical catalyzing amino acid residues (p.H88A and p.D89A) abrogated the capability of PLA2G10 to catalyze the production of arachidonic acid (AA), and also canceled the regulatory effects on cyclin E1 and CDK2 expression, as well as G1/S transition. In conclusion, PLA2G10 was a specific relapse-associated gene in STLMS. It facilitated the cell-cycle progression of STLMS cells at least by elevating the expression of cyclin E1 and CDK2. The hydrolytic activity was crucial for its oncogenic properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done., Methods: 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination., Results: At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls., Conclusions: Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.

Carbon dots (CDs) as new fluorescent materials with excellent fluorescence properties have shown enormous potential applications, especially in anticounterfeiting and cell imaging. Herein, nitrogen-doped CDs (NCDs) with excellent biocompatibility were prepared by a simple thermal sintering method. An extremely large red shift (∼130 nm) of the emission peak was observed when the excitation wavelength changes from 355 to 550 nm, indicating that NCDs are excellent fluorescent labeling materials for multiple cell imaging. On the other hand, NCDs showed obvious changes of emission intensity and peak position when the temperature increased from 223 to 323 K and the pH values changed from 1 to 13, respectively, which has been demonstrated by the "horse" pattern printed with NCD water-soluble fluorescent inks. The nontoxic NCDs dispersed in a multiple matrix are highly sensitive to excitation wavelength, temperature, and pH, indicating their great potential application in multiple anticounterfeiting and multiple cell imaging.

In this work, a series of novel chalcone derivatives bearing bispiperazine linker have been synthesized and in vitro anti-inflammatory, cytotoxic activity and anti-inflammatory mechanism have been screened. The results indicated that most bispiperazinochalcone derivatives displayed good inhibition of NO (IC 50  < 20 μM) and low cytotoxicity (CC 50  > 40 μM), and selectively inhibited the production of IL-1β via inhibiting NLRP3 inflammasome activation, as promising candidate compounds for the treatment of NLRP3 inflammasome-driven diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

As an increasing number of gene alterations have been discovered in intrahepatic cholangiocarcinoma (ICC), molecular targets are promising for the diagnosis and treatment of distinct subpopulations carrying unique molecular signatures. C-MET amplification is associated with a variety of tumors, including ICC; however, the characteristics of this alteration have not been assessed in ICC. By determining the ratios of C-MET/chromosome enumeration probe (CEP) 7 double-colour probes, we evaluated the presence of C-MET amplification in a cohort of 133 ICC tumors by fluorescence in situ hybridization (FISH). We further determined the levels of MET protein expression by immunohistochemistry (IHC) and analyzed clinicopathologic records. Of the samples, 21 (15.8 %) had high-frequency and 41 (30.8 %) had low-frequency C-MET genetic amplification, and 71 (53.4 %) had a normal C-MET gene. There were significant differences in gross classification (p = 0.045), microscopic cholangitis (p = 0.030), mucus level in tumors (p = 0.012) and T stage (p = 0.007) between the three groups. When we combined high-frequency and low-frequency amplifications of C-MET into one group, only microscopic cholangitis (p = 0.010) and stage (p = 0.016) showed significant differences compared to normal C-MET gene expression. However, when we combined the low-frequency C-MET amplification group with the normal C-MET group and compared this combined group with the high-frequency C-MET amplification group, the high-frequency group had more younger patients (p = 0.047), had more non-mass-forming (MF)-type cases according to gross classification (p = 0.015), secreted more mucus (p = 0.002) and appeared to have a higher T stage (p = 0.031) than the combined group. For IHC results, although only cluster C-MET amplification predicted protein overexpression, high-frequency amplification was associated with more protein expression than the other genetic statuses (p = 0.000). As low-frequency C-MET amplification exhibited similar biology to that of the normal gene, we regarded high-frequency amplification of C-MET as a unique molecular subtype. It may play important roles in tumor progression and may be used as a prognostic marker for targeted therapy., Competing Interests: Declaration of Competing Interest The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Endometriosis is a common gynecological disease characterized by the presence and growth of endometrial tissue outside the uterus, including the pelvis and abdominal cavity. This condition causes various clinical symptoms, such as non-menstrual pelvic pain, dysmenorrhea and infertility, seriously affecting the health and quality of life of women. To date, the specific mechanism and the key molecules of endometriosis remain uncertain. The purpose of the present study was to elucidate the mechanisms involved in the development and persistence of the disease. A number of mRNA expression profile datasets (namely GSE11691, GSE23339, GSE25628 and GSE78851) were downloaded from the Gene Expression Omnibus (GEO) database. These gene expression profiles were normalized, and the differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis. A total of 103 DEGs were screened upon excluding the genes that exhibited inconsistency of expression (P<0.05). Furthermore, the Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and construction of protein-protein interaction networks of DEGs were performed using online software. The results revealed that the DEGs were closely associated with cell migration, adherens junction and hypoxia-inducible factor signaling. In addition, immunohistochemical assay results were found to be consistent with the bioinformatics results. The present study may help us understand underlying molecular mechanisms and the development of endometriosis, which has a great clinical significance for early diagnosis of the disease., (Copyright: © Dai et al.)

Background: Bis(indolyl)methane derivatives are widely found in nature with a broad range of biological and pharmacological activities. The development of techniques for the synthesis and functionalization of bis(indolyl)methanes have attracted more and more attention in recent years., Objective: To study the synthesis and biological activity of heterocyclic substituted bis(indolyl)methanes., Materials and Methods: A series of heterocyclic substituted bis(indolyl)methanes (3a-3p) have been prepared by condensation reaction of indole and heterocyclic aldehydes catalyzed by boron trifluoride etherate with high yields. Preliminary in vitro anti-inflammatory in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and cytotoxic activity against human tumor cell lines (A549, Hela and SGC7901) by MTT assay were tested., Results: The result indicated that heterocyclic substituted bis(indolyl)methanes showed good antiinflammatory and selective cytotoxic activity. Especially, compounds 3o, 3p and 3q displayed similar inhibitory effect on the generation of NO to positive control dexamethasone, and compound 3q displayed similar selective cytotoxic activity to 5-FU., Conclusion: Heterocyclic substituted bis(indolyl)methanes may be used as potential anti-inflammatory and anticancer leads., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)